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Biomedical subjects

Masumi Ueda

Publications and source records attributed to Masumi Ueda.

8 recordsLinked to original sources

Aberrant localization of importin alpha1 in hippocampal neurons in Alzheimer disease.

Since many nuclear proteins are ectopically localized in the cytoplasm in the vulnerable neurons in Alzheimer disease (AD), we speculated that there is failure of the cytoplasmic-nuclear transport machinery in AD. In support of this notion, we found that importin alpha1, an essential component of cytoplasmic-nuclear transport, is abnormally accumulated in Hirano bodies in vulnerable hippocampal neurons in AD. These data suggest a hindrance in importin-mediated cytoplasmic-nuclear transport in AD.

Actins↗

Ectopic expression of phospho-Smad2 in Alzheimer's disease: uncoupling of the transforming growth factor-beta pathway?

Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, has been widely suggested to play a role in the pathogenesis of Alzheimer's disease. Supporting this, levels of TGF-beta are elevated in the cerebrospinal fluid, sera, and brain of patients with Alzheimer's disease. Since TGF-beta is neuroprotective, whereas Alzheimer's disease is typified by neurodegeneration, we speculated that defects in TGF-beta signaling might abrogate its neuroprotective properties. Consistently with an increase in TGF-beta in Alzheimer's disease, we found significant increases in phospho-Smad2, a major downstream signaling molecule of TGF-beta, in hippocampal neurons of Alzheimer's disease compared with age-matched control patients. However, in contrast to an expected nuclear localization, phosphorylated Smad2 in Alzheimer's disease was predominantly, and ectopically, found in the neuronal cytoplasm, specifically colocalized with neurofibrillary tangles and granulovacuolar degeneration. Given that a nuclear localization is required to regulate the transcription of TGF-beta target genes to afford neuroprotection, the ectopic localization of phosphorylated Smad2 suggests a defect in the Smad-mediated signaling pathway of TGF-beta in Alzheimer's disease and consequent loss of neuroprotective function.

Aged↗

A new procedure for experimental autoimmune uveitis with small uveitogenic peptides.

PURPOSE: Demonstration of experimental autoimmune uveitis (EAU) with extremely small, fragmented peptides (12-30 amino acid residues) of interphotoreceptor retinoid-binding protein (IRPB). METHOD: Very small fragmented peptides (no. 854, 888, 907, and 1057) were conjugated to heat-killed Group A Streptococcus cells and administered as a single intravenous injection to Lewis rats. A non-uveitogenic peptide 950 was also conjugated to heat-killed Streptococcus and administered. Administration of a mixture of small peptides and Streptococcus was a control for the peptides conjugated with Streptococcus. RESULTS: The uveitogenic peptide/Streptococcus conjugates produced uveitis inflammatory responses in the uvea, retina and pineal gland. Administration of mixtures of small peptides and Streptococcus cells, and a non-uveitogenic peptide 950 conjugated with Streptococcus did not produce autoimmune uveitis. CONCLUSIONS: Since mixtures of small uveitogenic peptides and Streptococcal cells did not develop autoimmune uveitis, conjugated Streptococcal cells provided a vehicle for macrophage phagocytosos of very small uveitogenic IRBP peptides. Subsequent antigen presentation from macrophages to lymphocytes developed autoimmune uveitis. Peptide 888, one of four IRBP peptides that encompass the major uveitogenic domain, proved to be the most effective in development of uveitis.

Animals↗

A 12-week structured education and exercise program improved climacteric symptoms in middle-aged women.

In the present study, 40- to 60-year-old women with climacteric symptoms were placed on a 12-week structured education and exercise program to ascertain the effects of this program on climacteric symptoms, quality of life (QOL), and attitude towards exercise. A total of 35 women served as subjects. Twenty women were enrolled in an educational and exercise program that involved learning about menopause and participating in physical activity at least three times a week (Group E). For comparison, the other 15 women did not participate in this program and were instructed to refrain from exercising during study period (Group C). The effects of the 12-week interventional program on climacteric symptoms, QOL, and attitude towards exercise were thereby investigated. The program demonstrated significant effects on climacteric symptoms in terms of Kupperman index and psychosomatic symptoms, especially paresthesia and nervousness. In other words, climacteric symptoms improved significantly in Group E. Furthermore, scores for QOL and attitude towards exercise improved in Group E after the 12-week program; however, these trends did not reach statistical significance. Hence, the 12-week structured education and exercise program was shown to be effective in alleviating climacteric symptoms.

Adult↗

Structures of 1,4-benzodioxane derivatives from the seeds of Phytolacca americana and their neuritogenic activity in primary cultured rat cortical neurons.

The methanol extract of the seeds of Phytolacca americana was reinvestigated to yield three new 1,4-benzodioxane-type compounds, americanoic acid methyl ester (1), isoamericanoic acid A methyl ester (2), and 9'-O-methylamericanol A (3) along with the previously isolated neolignans 6-9. The structures of 1-3 were characterized by 2D NMR and long-range selective proton-decoupling (LSPD) techniques. The neuritogenic effects of compounds 1-3, and dicarboxilic acids 4 and 5, which had been previously synthesized with horseradish peroxidase-catalyzed oxidative coupling of caffeic acid, were examined in primary cultured rat cortical neurons. Americanoic acid A methyl ester (1) exhibited neurite outgrowth-promoting activity at concentration of 0.01-1.0 microM, whereas dicarboxilic acids 4 and 5 were found to induce neuritogenesis dose dependently at the concentrations from 0.1 microM to 10 microM.

Animals↗

Multiparticulate chitosan-dispersed system for drug delivery.

A multiparticulate chitosan-dispersed system (CDS), which is composed of the drug reservoir and the drug release-regulating layer, was developed for drug delivery. The drug release-regulating layer is a mixture of water-insoluble polymer and chitosan powder. The drug is released from CDS pellets in all regions of the gastrointestinal tract (from the stomach to the colon). CDS pellets containing chitosan powder were designed to dissolve chitosan powder partly in the release-regulating layer in the stomach and release part of drug. After passing through the stomach, the drug is released from CDS pellets at a constant speed in the small intestine. In the large intestine, CDS pellets were designed to disintegrate the remaining chitosan powder at an accelerated speed and the remaining drug in CDS pellets is released. The drug release rate can be controlled with the thickness of the chitosan-dispersed water-insoluble layer. Furthermore, for colon-specific drug delivery, an additional outer enteric coating is necessary to prevent drug release from CDS pellets in the stomach, because the chitosan-dispersed water-insoluble layer dissolves gradually under acidic conditions. The resulting enteric-coated CDS (E-CDS) pellets were found to permit colon-specific drug delivery. In this study, the multiparticulate CDS was adopted not only for colon-specific drug delivery but also for sustained drug release.

Acetaminophen↗

Chitosan dispersed system for colon-specific drug delivery.

A chitosan dispersed system (CDS), which was composed of active ingredient reservoir and the outer drug release-regulating layer dispersing chitosan powder in hydrophobic polymer, was newly developed for colon-specific drug delivery. An aminoalkyl methacrylate copolymer RS (Eudragit) RS) was selected as a hydrophobic polymer because it is hardly dissolved in acidic medium in which easily dissolves chitosan. In order to obtain the bi-functional releasing characteristics, i.e. time dependent and site specific, capsules containing the active ingredient (Drug Capsules) were coated by the chitosan dispersed hydrophobic polymer, resulting in CDS Capsules. The release rate could be controlled by changing the thickness of the layer. Furthermore, for colon-specific drug delivery, an additional outer enteric coating was necessary to prevent the drug release from CDS Capsules in the stomach, since chitosan dispersed in the layer dissolves easily under acidic conditions. Resultant enteric-coated CDS Capsules reached the large intestine within 1-3 h after oral administration and they were degraded at the colon in beagle dogs.

Acetaminophen↗

Design of controlled release system with multi-layers of powder.

Pellets containing active ingredients were coated with water-insoluble powders, i.e. hydrogenated caster oil (Lubliwax (WAX)) and magnesium stearate (Mg-St). The influences of the structural difference of the sustained release layer and curing conditions on the drug release rate were investigated. Sodium valproate (VP-Na) was used as a highly water-soluble model drug. Drug release profiles were influenced by the combination of the WAX layer and the Mg-St layer. Even if the formula of sustained release layers were the same, drug release rate could be affected by the structural difference of the controlled release layer. The Mg-St layer was more effective in prolonging drug release than the WAX layer. Compared with single and double layer types, the triple layer (sandwich) type was most effective in obtaining a long sustained drug release. Heat-treatment retarded drug release mainly by increasing the density of the sustained release layer of the WAX. The Mg-St was effective in protecting the agglomeration between particles during heat-treatment. Optimal heat-treatment conditions were found to exist. Scanning electron microscopy (SEM) analysis indicated that heat-treatment caused the WAX to melt, formed a film-like structure and made the release layer dense. Furthermore, heat-treatment changed the release pattern of VP-Na from sustained release pellets with a multi-layer of powder, leading to zero-order release.

Delayed-Action Preparations↗